Aphasia, Primary Progressive

引言ST段抬高型心肌梗死患者经皮冠状动脉介入治疗后，手术后抗凝(PPA)经常被应用，尽管没有确凿的数据支持这种做法。2024年2月26日，首都医科大学聂绍平及法国索邦大学Gilles Montalescot共同通讯在Circulation(IF 38)在线发表题为“Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for STSegment-Elevation Myocardial Infarction: A Multicenter, Randomized, Double-Blind Trial”的研究论文，该研究进行了一项经皮冠状动脉介入治疗ST段抬高型心肌梗死术后抗凝的多中心、随机、双盲试验。在2019年1月10日至2021年9月18日期间，共有2989名患者被随机分组。PPA组和安慰剂组均有37例患者(2.5%)达到主要疗效终点(风险比为1.00 [95% CI, 0.63至1.57])。PPA组和安慰剂组出血发生率无差异(8例[0.5%]vs 11例[0.7%]);风险比，0.74 [95% CI, 0.30 ~ 1.83])。因此，经皮冠状动脉介入治疗后常规PPA是安全的，但不能减少30天缺血事件。ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)后，术后抗凝(PPA)经常用于预防缺血或血栓事件。然而，关于常规PPA的有效性、安全性和最佳方案的数据很少。尽管美国指南没有提到STEMI的PPA治疗，但最近欧洲心脏病学会关于急性冠状动脉综合征管理的指南建议在侵入性手术后停用抗凝剂，但证据为C级，且未提及原发性PCI。先前对比伐卢定的研究表明，PPA(联合比伐卢定或未分离肝素[UFH]，联合或不联合糖蛋白IIb/IIIa抑制剂)并不能减少不良的缺血事件，但会增加出血并发症，而另一项对急性冠状动脉综合征的分析报告称，高剂量比伐卢定给予长达4小时，可能对缺血有益，而不会出血过多。在ATOLL研究中(在短期和长期随访中，急性心肌梗死接受初级血管成形术和静脉注射依诺肝素或未分割肝素治疗以降低缺血和出血事件)，首次PCI术后单剂量40mg每日一次延长依诺肝素抗凝治疗时间，但没有随机评价PPA的效果。使用来自中国心血管疾病改善护理中心(CCC-ACS)的真实数据，研究人员发现PPA与院内死亡率降低相关，且没有过多的大出血并发症RIGHT试验(初次PCI后STEMI患者抗凝延长与不抗凝的比较)旨在测试当代STEMI初次PCI后常规PPA是否优于不抗凝。在所有患者进行首次PCI手术期间使用比伐卢定后，对可用于PPA的3种抗凝药物与各自的安慰剂进行评估。术后抗凝与安慰剂组的主要疗效和安全性结果（Credit: Circulation）在STEMI患者中，首次PCI后至少48小时的低剂量PPA在降低30天缺血结局方面并不优于不抗凝。在一项预先指定的探索性分析中，使用不同的抗凝方案(依诺肝素、UFH和比伐卢定)在主要疗效终点显示出不同的治疗效果，依诺肝素与安慰剂相比可能有益处。PPA患者未出现过量出血，证实了首次PCI术后48小时内减少抗凝剂剂量的安全性。该研究的结果也与之前在比伐卢定研究中获得的结果一致，包括最近的一项试验，在PCI术后相对较短的比伐卢定输注(1.75 mg·kg·h，最多4小时)，研究人员在随机化之前使用了这项试验。与另一项当代试验相比，该研究观察到糖蛋白IIb/ IIIa抑制剂的紧急使用发生率更高，可能是由于研究地点的使用分布不均匀。研究人员也承认抗血栓治疗强度对缺血和出血事件发生率的影响，该研究在使用糖蛋白IIb/IIIa抑制剂后的随机化过程确保了在主要疗效和安全性终点方面评估PPA与安慰剂的可比设计。总的来说，首次PCI术后常规PPA使用低剂量抗凝是安全的，但不能改善30天的缺血结局。数据表明，抗凝剂在预防30天缺血事件方面可能存在差异，但这一发现需要在未来的研究中得到证实。原文链接https://doi-org.libproxy1.nus.edu.sg/10.1161/CIRCULATIONAHA.123.067079责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文Nature | 癌症与神经系统的致命舞蹈

Language-processing difficulties are more of an indicator than memory loss of amnestic mild cognitive impairment (aMCI), a risk factor for dementia due to Alzheimer's disease, according to a new study. Individuals with mild cognitive impairment, especially of the "amnestic subtype" (aMCI), are at increased risk for dementia due to Alzheimer's disease relative to cognitively healthy older adults. Now, a study co-authored by researchers from MIT, Cornell University, and Massachusetts General Hospital has identified a key deficit in people with aMCI, which relates to producing complex language. This deficit is independent of the memory deficit that characterizes this group and may provide an additional "cognitive biomarker" to aid in early detection -- the time when treatments, as they continue to be developed, are likely to be most effective. The researchers found that while individuals with aMCI could appreciate the basic structure of sentences (syntax) and their meaning (semantics), they struggled with processing certain ambiguous sentences in which pronouns alluded to people not referenced in the sentences themselves. "These results are among the first to deal with complex syntax and really get at the abstract computation that's involved in processing these linguistic structures," says MIT linguistics scholar Suzanne Flynn, co-author of a paper detailing the results. The focus on subtleties in language processing, in relation to aMCI and its potential transition to dementia such as Alzheimer's disease is novel, the researchers say. "Previous research has looked most often at single words and vocabulary," says co-author Barbara Lust, a professor emerita at Cornell University. "We looked at a more complex level of language knowledge. When we process a sentence, we have to both grasp its syntax and construct a meaning. We found a breakdown at that higher level where you're integrating form and meaning." The paper, "Disintegration at the syntax-semantics interface in prodromal Alzheimer's disease: New evidence from complex sentence anaphora in amnestic Mild Cognitive Impairment (aMCI)," appears in the Journal of Neurolinguistics. The paper's authors are Flynn, a professor in MIT's Department of Linguistics and Philosophy; Lust, a professor emerita in the Department of Psychology at Cornell and a visiting scholar and research affiliate in the MIT Department of Linguistics and Philosophy; Janet Cohen Sherman, an associate professor of psychology in the Department of Psychiatry at Massachusetts General Hospital and director of the MGH Psychology Assessment Center; and, posthumously, the scholars James Gair and Charles Henderson of Cornell University. Anaphora and ambiguity To conduct the study, the scholars ran experiments comparing the cognitive performance of aMCI patients to cognitively healthy individuals in separate younger and older control groups. The research involved 61 aMCI patients of Massachusetts General Hospital, with control group research conducted at Cornell and MIT. The study pinpointed how well people process and reproduce sentences involving "anaphora." In linguistics terms, this generally refers to the relation between a word and another form in the sentence, such the use of "his" in the sentence, "The electrician repaired his equipment." (The term "anaphora" has another related use in the field of rhetoric, involving the repetition of terms.) In the study, the researchers ran a variety of sentence constructions past aMCI patients and the control groups. For instance, in the sentence, "The electrician fixed the light switch when he visited the tenant," it is not actually clear if "he" refers to the electrician, or somebody else entirely. The "he" could be a family member, friend, or landlord, among other possibilities. On the other hand, in the sentence, "He visited the tenant when the electrician repaired the light switch," "he" and the electrician cannot be the same person. Alternately, in the sentence, "The babysitter emptied the bottle and prepared the formula," there is no reference at all to a person beyond the sentence. Ultimately, aMCI patients performed significantly worse than the control groups when producing sentences with "anaphoric coreference," the ones with ambiguity about the identity of the person referred to via a pronoun. "It's not that aMCI patients have lost the ability to process syntax or put complex sentences together, or lost words; it's that they're showing a deficit when the mind has to figure out whether to stay in the sentence or go outside it, to figure out who we're talking about," Lust explains. "When they didn't have to go outside the sentence for context, sentence production was preserved in the individuals with aMCI whom we studied." Flynn notes: "This adds to our understanding of the deterioration that occurs in early stages of the dementia process. Deficits extend beyond memory loss. While the participants we studied have memory deficits, their memory difficulties do not explain our language findings, as evidenced by a lack of correlation in their performance on the language task and their performances on measures of memory. This suggests that in addition to the memory difficulties that individuals with aMCI experience, they are also struggling with this central aspect of language." Looking for a path to treatment The current paper is part of an ongoing series of studies that Flynn, Lust, Sherman, and their colleagues have performed. The findings have implications for potentially steering neuroscience studies toward regions of the brain that process language, when investigating MCI and other forms of dementia, such as primary progressive aphasia. The study may also help inform linguistics theory concerning various forms of anaphora. Looking ahead, the scholars say they would like to increase the size of the studies as part of an effort to continue to define how it is that diseases progress and how language may be a predictor of that. "Our data is a small population but very richly theoretically guided," Lust says. "You need hypotheses that are linguistically informed to make advances in neurolinguistics. There's so much interest in the years before Alzheimer's disease is diagnosed, to see if it can be caught and its progression stopped." As Flynn adds, "The more precise we can become about the neuronal locus of deterioration, that's going to make a big difference in terms of developing treatment." Support for the research was provided by the Cornell University Podell Award, Shamitha Somashekar and Apple Corporation, Federal Formula Funds, Brad Hyman at Massachusetts General Hospital, the Cornell Bronfenbrenner Center for Life Course Development, the Cornell Institute for Translational Research on Aging, the Cornell Institute for Social Science Research, and the Cornell Cognitive Science Program.

Speech-Language Pathologists Can Help by Providing Strategies to Patients and Care Partners That Improve Quality of Life ROCKVILLE, Md., Feb. 22, 2024 /PRNewswire/ -- With primary progressive aphasia (PPA) once again in the spotlight following news of Wendy Williams' recent diagnosis, the American Speech-Language-Hearing Association (ASHA) is sharing information about the signs of PPA, how it differs from other conditions, and how speech-language pathologists (SLPs) can help families improve communication with—and overall quality of life for—loved ones who are diagnosed. Continue Reading What Is PPA? PPA is a rare and lesser-known neurological condition. It is caused by changes in the frontal and temporal lobes of the brain, which are largely responsible for language and executive functioning. These areas also act as the body's center for making decisions and navigating daily life and activities. PPA is a rare and lesser-known neurological condition. Post this PPA is more likely to occur in people in their 40s to 60s. There is no cure or direct treatment, but SLPs can help people manage the changes that occur in communication and thinking—and put supports and care plans in place for addressing the progression of the disease (see "How SLPs Can Help," below). How Is PPA Different From Other Conditions? PPA is not the same as the following diseases or conditions: Aphasia caused by stroke or other brain injuries. PPA is progressive, so the communication challenges may start slowly—not suddenly—and will get worse over time. Alzheimer's disease and other forms of dementia, where memory changes are the earliest and most recognizable differences. PPA primarily impacts language and communication skills as the earliest signs. Depression or anxiety, although some of the communication or behavioral changes may be similar. Someone with PPA who has trouble interacting with others may socially withdraw or show changes in personality, which can lead to an early but inaccurate diagnosis of mental health disorders. Communication Changes With PPA Some common communication changes that people with PPA may experience early in the disease include: talking or signing slower than usual; having difficulty thinking of words, even the names of familiar objects and people; leaving words out or mixing up the order of words in sentences; using a different word than the one they mean (e.g., "table" instead of "chair"); having difficulty understanding what words mean; struggling to follow a conversation; and/or making mistakes in spelling that they wouldn't typically make. How SLPs Can Help SLPs help by learning an individual's communication priorities early—and then putting systems in place that are supportive as the disease progresses. PPA affects the whole family. Consequently, SLP services extend beyond the person with PPA. They include any or all of the following: Explaining the communication changes that a person is experiencing—and finding strategies that support their participation in the things they want, need, and love to do. Introducing communication strategies and tools that may not be needed today but will be in the future—so that they are well established before the person needs them. Pairing different communication situations with different strategies, like using quick gestures or other signals for medical needs and recording the person's speech for later use for personal messages like their favorite dad jokes and bedtime stories. Working with the person's family and friends to be supportive communication partners—and adapting to changes as they occur. Empowering the person to advocate for their communication needs everywhere they go—and helping connect the person with resources and new communities. Helping a person maintain effective communication, which may look different as their condition progresses. How Families Can Support Communication People with PPA may be unable to fully realize their communication challenges. It's important for loved ones to continue to include the person in conversations and decision making. Tips for how to do that include the following: Validate frustrations, and use supports like writing or drawing to make the interaction more successful. Communication breakdowns are particularly hard for people in the earlier stages of the disease. Slow down when you are speaking with someone who has PPA. Use direct language, and keep sentences short. Give the person time to communicate (rather than finishing the sentence for them). Add nonverbal cues to your speech (e.g., pointing to an object while asking a question about it) if a person's understanding is affected. Avoid open-ended questions, and provide choices to pick from. Break down directions into small steps. Find an SLP at . Media Contact: Francine Pierson, 301-296-8715 SOURCE American Speech-Language-Hearing Association (ASHA)